A year and a half ago, a cryptic NASA press release focused attention on what it promised would be new evidence in the hunt for life on alien worlds. NASA and the journal involved (Science) sat on the results for days as rumors built. Eventually, the paper debuted: NASA scientists had found evidence that life on Earth could rely on alternate chemistry, one that replaced the phosphorus used in many biomolecules for a chemical relative that is usually toxic: arsenic.

Controversy did not end there. Researchers quickly identified a number of holes in the initial analysis, both logical and experimental. Less than six months later, Science published a series of responses to the original paper that raised significant questions about its accuracy. Now, the topic is back in the pages of the same journal. Two labs have obtained the original arsenic-tolerant bacteria and shown that some of the original paper's conclusions are completely off-base.

The bacteria themselves were originally obtained from California's Mono Lake, which naturally contains high levels of arsenic. Over multiple generations in the lab, scientists forced them to evolve further, gradually ramping up the arsenic concentrations while lowering the amount of phosphorus available to the organisms. After enough generations, the resulting bacteria reportedly had some rather exceptional properties: they could get by without having any phosphorus added to their growth media, but only if arsenic were added. And, possibly as part of that adaptation, the arsenic started appearing with biomolecules that normally contain phosphorus (although, as our initial coverage noted, the data didn't indicate how the arsenic was being used).

The responses suggested a couple of problems with the work. On purely theoretical grounds, we know that arsenate compounds should spontaneously fall apart in water. This makes their apparent presence in biomolecules difficult to accept. And, on purely practical grounds, it turns out to be really difficult to get rid of all the phosphorus from the other lab chemicals scientists typically rely on. That suggests these bacteria weren't really doing without the stuff.

The new papers, from groups in Zurich and Vancouver, nail down a lot of loose ends. The material suggests that the initial results were a mix of artifact and not pushing the experiments sufficiently far.

First, the inability to grow without phosphate. The Zurich group shows that these organisms can survive down to remarkably low amounts of phosphorus—the equivalent of adding 0.000162 grams for every liter of liquid growth medium (for those of you hung up on English units, that's "almost nothing"). But if you use ultrapure materials that drop the phosphorus levels down to below what the team could detect (somewhere less than 20 percent of that level), the bacteria won't grow. They still need phosphate.

The original paper reported that when phosphate starved, the organisms needed arsenic in their media to grow at all. But the Vancouver group found that wasn't the case. They suggest this was an artifact: the bacteria also had a requirement for a specific amino acid, something that was not reported in the original paper. They suspect that the arsenic solution used in the original experiments had been contaminated with the amino acid, explaining its apparent requirement.

So the bacteria don't appear to require arsenic. But, just as clearly, they can tolerate extremely high levels of the substance, and there was evidence that it is incorporated into biomolecules, including DNA. The new papers tackle this as well. The Zurich group used a technique called mass spectrometry, in which every chemical in the cell is separated based on how much an individual molecule weighs. The results can be compared to a database of known weights to identify most molecules very specifically. In this case, the authors updated their database to include molecules with phosphate replaced by arsenate.

The results largely came back blank. Some arsenate was associated with sugars, but this apparently formed spontaneously, without the need for any biochemical activity. If you let the standard lab bacteria E. coli grow in a medium containing some arsenic, they formed all of these compounds as well. This suggests they have nothing to do with a newly evolved tolerance to arsenic.

The Vancouver group focused on the reported association of arsenic with DNA, a phosphate-rich molecule. That makes DNA a great candidate for detecting even a rare substitution of arsenate for phosphate, a change that should make the DNA sensitive to breaking down in a simple solution of water. But, even after extended storage in water, DNA obtained from these bacteria was as stable as that obtained from the same strain grown without arsenic. Based on the groups' measurements, that means that less than one-in-25,000 phosphates could possibly be swapped out.

Given all this data, it's hard to argue with the Vancouver team's conclusion: "The end result is that the fundamental biopolymers conserved across all forms of life remain, in terms of chemical backbone, invariant."

But an argument may be brewing. MSNBC's Alan Boyle has been communicating with the team behind the original findings, and they suggest there's a paper in the works that backs up their initial findings. Although the two new publications seem like the final word on the topic, more appears to be forthcoming.

Arsenic and open science

The researcher who led the Vancouver group, Rosie Redfield, deserves special mention in this saga. Redfield has embraced blogging as part of the scientific process, and was one of the first researchers to publicly raise doubt about the original arsenic results. Her doubts caught the attention of science journalists and led to some of the first skeptical coverage. Once she obtained the bacteria and started working on them, she put results up on her blog as they came in. As she prepared her paper for publication, she also put draft versions up on the arXiv. That is common in physics and astronomy, but almost unheard of in biology.

Not only is Redfield pushing her fellow biologists for greater openness, she has apparently pushed the journals as well. Science normally distributes papers that will be released in a given week to the press on Sunday night, but asks the press to hold them for a Thursday embargo. Redfield was scheduled to speak at an evolution meeting last night, and let the editors of Science know that her arsenic work would be the topic (and, naturally, she blogged about letting them know, too). In response, Science made these two papers available without restrictions last night.

Had Science been equally responsible with its embargo of the initial results from NASA, some of the hype that developed in response to the uncertainty might never have become a problem in the first place.

Yeah, Science is a pretty crappy journal. It's no surprise they published the original findings without checking them out first. They like the pop-science articles - whether they're right or wrong...

The only problem with this whole saga was NASA's hare brained press department. They took a preliminary finding and hyped it to hell and back again. The senior scientists in the group should have squashed the hyperbole until additional experiments were performed - there were really a number of obvious controls that were omitted from the initial paper.

And perhaps Science jumped the gun. Your characterization of them as 'crappy' is just snark on your part. But it was an interesting finding and in the end, the scientific process worked well. Unfortunately, it is going to damage the reputation of a number of people unless their new research can overcome this new mass spec and more careful phosphate analysis, but that's the risk when you publish.

Bottom line - PR departments should be kept in a dark closet and let out only under carefully controlled circumstances.

I think the science is pretty clear. I can't see what Wolfe-Simon will come up with, her original response when she was criticized was the same one of cell-death. Which I believe at least the Vancouver group has controlled for, IIRC.

The "not the same conditions" and "extraordinary claims gets criticized" is the sign of pathological science that she has been painted with before.

- The other groups reproduced the same behavior (initial growth rates) by finding out that there was a lack of phosphorous and, perhaps, an amino acid that wasn't controlled for originally. Experiments need to be reproducible, or they won't be useful.

- If criticism is a problem, it was because she had forgotten the other side of the coin: "extraordinary claims needs extraordinary evidence". They didn't even come up with _ordinary_ foolproof evidence.

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MSNBC's Alan Boyle has been communicating with the team behind the original findings,

It is unclear if from the linked article that the emailed Wolfe-Simon gets support from her original team, she has been severed and not supported by them, and her "we" is a generic term.

On to the the science context in weird politics:

- I don't think much of this work. It originated by Paul Davies et al taking an interest in astrobiology, and it was sloppy work.

Davies is a Templeton-funded deist, and his ideas of "a shadow biosphere" is not very biologically likely. The universal common ancestor of all observed cellular and viral life is the best observed fact of all of science, with ~ 10^2000 against multiple ancestors by way of the common genetic code.

I assume his interest in trying to observe alternate biochemistries derives from the idea that it makes life elsewhere more possible and by that roundabout human analogs more special. 'Therefore gods exist.'

But both of these are common biological hypotheses (evolving populations is easy, evolving traits is very constrained - see the uniqueness of the Elephantidae trunk. They certainly has no connection with Davies stated ultimate interests in understanding nature.

- But while Redfield is to applaud for much (criticism, openness, using arxiv, using web based research), and her results stands for themselves, her motives comes across as unscientific as well.

She seems motivated by astrobiologists encroaching on her area. Granted, they overstepped here, she knows more of how to do research on bacteria than geochemist Wolfe-Simon and, it seems, the rest of the original team. But I wish she would take the competition, as it were, in good spirit as founded in curiosity in nature.

@ molson3:

Ooh, snarky. Of course journals don't do original research but use peer review and welcome responses for checking. Which they did both of.

Huh -- those organisms sounded pretty cool. Oh, well, the truth is what's important. And PR departments are part of the problem, but the other part is pop-science editors (not here at Ars, but some elsewhere) who take a story with a supposition or two at the end and turn them into what sounds like near-certainties.

Yeah, I guess I was a little snarky before, but the last few articles in Science that were in my field were horrible at best. I don't think they know who is qualified to peer review articles in some fields...

- But while Redfield is to applaud for much (criticism, openness, using arxiv, using web based research), and her results stands for themselves, her motives comes across as unscientific as well.

She seems motivated by astrobiologists encroaching on her area. Granted, they overstepped here, she knows more of how to do research on bacteria than geochemist Wolfe-Simon and, it seems, the rest of the original team. But I wish she would take the competition, as it were, in good spirit as founded in curiosity in nature.

Sounds quite scientific to me. A group of people with an agenda (both personal and NASA's we need to prove alien life is likely to be near enough to justify our research budget) and no experience of the field start doing poorly planned experiments on their own without the support of a collaborative effort. Surprise, surprise, they make a complete hash of it. "Fools rush in" comes to mind... So she is, in my opinion, quite right to take offence - scenarios such as this have been the cause of some of the worst science ever published since the pitfalls of research in a field are learnt by experience.

I'm curious how they clean their glassware. If it's standard autoclave, I can see some phosphates surviving the treatment. That technique is meant to kill not remove residual salts. If I were to be part of repeatability study, I'd use standard base bath treatment on all the glassware (done in typical academic chemical labs). That and reverse osmotically treated water as a source for all solutions. That'll take care of any phosphates issues.

Science itself is a decent journal, at least on the chemistry side of it. All publications should be taken with a grain of salt and good scrutiny. Even the best journals sometimes publish crap. It's all about reading the article and figuring out that something isn't right. This is business as usual.

That the article gained media traction is the issue. Media jumps on the wagon and assumes that if it is published it is accepted fact, and that is a patently false attitude to take with the literature.

It is unclear if from the linked article that the emailed Wolfe-Simon gets support from her original team, she has been severed and not supported by them, and her "we" is a generic term.

FWS has a new "team" - she is now in John Tanier's lab. Tanier is a very successful structural biologist and I'm blown away by how much he's gone "all-in" on FWS' shenanigans. From the Washington Post:

Quote:

He said the authors of the two new papers “may well regret some of their statements” in the future.

“There are many reasons not to find things — I don’t find my keys some mornings,” he said. “That doesn’t mean they don’t exist. The absence of a finding is not definitive.”

I'm curious how they clean their glassware. If it's standard autoclave,

Uh, autoclaves sterilize, not clean. Any microbiologist would know that (but apparently not chemists!). Likewise, reverse-osmosis purified water is standard practice.

Quote:

It's all about reading the article and figuring out that something isn't right. This is business as usual.

I think it's been clearly established that this paper wasn't properly peer-reviewed. That's the problem with Science (the journal) - they want to hype the stuff they publish to sell ads, among other things.

Yeah, Science is a pretty crappy journal. It's no surprise they published the original findings without checking them out first. They like the pop-science articles - whether they're right or wrong...

That's junk on your part. I doubt you ever read most of the articles. I've been a member of the AAAS since 1969. Science is highly respected. But with the thousands of articles that get published, a few slip though.

I'm not surprised at the new statements made over the findings. I thought it highly unlikely that arsenic would be capable of substituting. Not quite as bad as those who think silicon could be capable of supporting life in place of carbon, but still very unlikely.

I'm curious how they clean their glassware. If it's standard autoclave, I can see some phosphates surviving the treatment. That technique is meant to kill not remove residual salts. If I were to be part of repeatability study, I'd use standard base bath treatment on all the glassware (done in typical academic chemical labs). That and reverse osmotically treated water as a source for all solutions. That'll take care of any phosphates issues.

Science itself is a decent journal, at least on the chemistry side of it. All publications should be taken with a grain of salt and good scrutiny. Even the best journals sometimes publish crap. It's all about reading the article and figuring out that something isn't right. This is business as usual.

That the article gained media traction is the issue. Media jumps on the wagon and assumes that if it is published it is accepted fact, and that is a patently false attitude to take with the literature.

FWS has a new "team" - she is now in John Tanier's lab. Tanier is a very successful structural biologist and I'm blown away by how much he's gone "all-in" on FWS' shenanigans. From the Washington Post:

That article quotes Redfield as saying:

"“A very flawed paper was published and received an inordinate amount of publicity,” she wrote in an e-mail. “But other researchers responded very quickly. . . . Now refutations of the work by two independent research groups are appearing in the same high-profile journal, and the refutations are being well publicized. This is how science is supposed to work.”"

I'm not sure that loud-mouthed, strongly-worded claims by all sides of a debate is how science is 'supposed to work'. Redfield is just as guilty of seeking 'an inordinate amount of publicity' as the original NASA press release (and possibly Wolfe-Lopez) was.

I'm not sure that loud-mouthed, strongly-worded claims by all sides of a debate is how science is 'supposed to work'. Redfield is just as guilty of seeking 'an inordinate amount of publicity' as the original NASA press release (and possibly Wolfe-Lopez) was.

Fight fire with fire? Personally I don't care whether FWS, Tanier, Redfield or any other scientist are attention seekers. I do care what claims they're making and what evidence they have to back it up. Everything else is a distraction.

Redfield is just as guilty of seeking 'an inordinate amount of publicity'

Did Rosie submit the first paper? Seems to me that she blogged about it, and your can either read about her work or not. That the response came in Science, is because the original paper came out in that journal.

Did nobody follow this when the original came out last year? At the time Science recognized that the original article was not the end of the story and took the unusual step of publishing both an Editor's Note ("...the discussion published today is only a step in a much longer process. Wolfe-Simon et al. are making bacterial strain GFAJ-1 available for others (2) to test their hypotheses in the usual way that science progresses.") and a series of Technical Comments (= criticisms) in the exact same issue.

I think the original paper and "Science" is being hammered too hard. First the paper is original! (at least seemingly so) And opens a highly interesting question, exactly how do the bacteria handle this arsenic something the follow up does not attempt to address. I don't know what it's like in the field of biology, but in physics in math opening up interesting and important questions is often as valued as closing them.

I think the original paper and "Science" is being hammered too hard. First the paper is original! (at least seemingly so) And opens a highly interesting question, exactly how do the bacteria handle this arsenic something the follow up does not attempt to address. I don't know what it's like in the field of biology, but in physics in math opening up interesting and important questions is often as valued as closing them.

The original paper didn't open up any interesting questions (the questions it addressed had been in the literature for a long, long time). It also didn't answer the question of how "the bacteria handle this arsenic". It did make some big claims from some shoddy work, however. Does physics and math publish stuff like that?

Redfield is just as guilty of seeking 'an inordinate amount of publicity'

Did Rosie submit the first paper? Seems to me that she blogged about it, and your can either read about her work or not. That the response came in Science, is because the original paper came out in that journal.

In addition to her strident criticism on her blog (whether merited or not), it's conclusions like these in formal papers that reek of attention seeking:

"the fundamental biopolymers conserved across all forms of life remain, in terms of chemical backbone, invariant."

While par for the course for Science, formal papers should not make absolute-ish statements like that. Blog? OK. Journal paper. Not OK.

In that regard, Tainer's comments about missing car keys != non-existent keys is spot on (as a general critique). In this particular case, the car keys (arsenic-containing DNA) may actually not exist, but we don't know that to an absolute certainty.

Just goes to show that if you have incredible findings and claims, that you had better work harder and smarter then everyone else to try to falsify your hypothesis before telling the entire scientific community and having them do it for you... very, very publicly. Fame is great and all, but you don't want the rest of the world correcting your mistakes in public journals.

Just goes to show that if you have incredible findings and claims, that you had better work harder and smarter then everyone else to try to falsify your hypothesis before telling the entire scientific community and having them do it for you... very, very publicly. Fame is great and all, but you don't want the rest of the world correcting your mistakes in public journals.

Redfield is just as guilty of seeking 'an inordinate amount of publicity'

Did Rosie submit the first paper? Seems to me that she blogged about it, and your can either read about her work or not. That the response came in Science, is because the original paper came out in that journal.

In addition to her strident criticism on her blog (whether merited or not), it's conclusions like these in formal papers that reek of attention seeking:

"the fundamental biopolymers conserved across all forms of life remain, in terms of chemical backbone, invariant."

While par for the course for Science, formal papers should not make absolute-ish statements like that. Blog? OK. Journal paper. Not OK.

In that regard, Tainer's comments about missing car keys != non-existent keys is spot on (as a general critique). In this particular case, the car keys (arsenic-containing DNA) may actually not exist, but we don't know that to an absolute certainty.

With that partial quote I would agree, but the full quote would be ""The end result is that the fundamental biopolymers conserved across all forms of life remain, in terms of chemical backbone, invariant."

I have no trouble with that. The original Wolfe-Simon et al. claimed to have found variance in that chemical backbone. This paper shows that there is no proof of such variance. They don't say that its absolutely super-impossible that such variance would exist, just that the evidence doesn't support such conclusions. The major biopolymers indeed remain invariant in basic chemical structure.

I think the original paper and "Science" is being hammered too hard. First the paper is original! (at least seemingly so) And opens a highly interesting question, exactly how do the bacteria handle this arsenic something the follow up does not attempt to address. I don't know what it's like in the field of biology, but in physics in math opening up interesting and important questions is often as valued as closing them.

The original paper didn't open up any interesting questions (the questions it addressed had been in the literature for a long, long time). It also didn't answer the question of how "the bacteria handle this arsenic". It did make some big claims from some shoddy work, however. Does physics and math publish stuff like that?

I didn't say it answered the "question". Just opened it, . Now you say it didn't open it. Citation? I still hate the tone of this criticism. Ultimately there is no harm with a bit of over enthusiasm on the part of researchers especially after publication of their work in "Science", even if every conclusion was incorrect. In a sense this over enthusiasm only invites closer peer review, helping us get to the truth, which is the only thing that matters. The tone of criticism is abhorent.

I didn't say it answered the "question". Just opened it, . Now you say it didn't open it. Citation?

The only question the paper opened was whether or not their conclusions could be drawn from their shoddy work. The question of which elements are required for life and how they're used has a very long history and this work opened nothing new. Search PubMed if you don't believe me.

Quote:

helping us get to the truth, which is the only thing that matters. The tone of criticism is abhorrent.

If the truth is the only thing that matters, then why are you arguing that the tone of criticism also matters?

Hmm, that's in isolation, not in organisms, which have many tricks up their sleeve. "a few species of bacteria are able to use arsenic compounds as respiratory metabolites." -http://en.wikipedia.org/wiki/Arsenic

- But while Redfield is to applaud for much (criticism, openness, using arxiv, using web based research), and her results stands for themselves, her motives comes across as unscientific as well.

She seems motivated by astrobiologists encroaching on her area. Granted, they overstepped here, she knows more of how to do research on bacteria than geochemist Wolfe-Simon and, it seems, the rest of the original team. But I wish she would take the competition, as it were, in good spirit as founded in curiosity in nature.

Sounds quite scientific to me. A group of people with an agenda (both personal and NASA's we need to prove alien life is likely to be near enough to justify our research budget) and no experience of the field start doing poorly planned experiments on their own without the support of a collaborative effort. Surprise, surprise, they make a complete hash of it. "Fools rush in" comes to mind... So she is, in my opinion, quite right to take offence - scenarios such as this have been the cause of some of the worst science ever published since the pitfalls of research in a field are learnt by experience.

Yes, that is the laudable part, the criticism. I was questioning her motivations, since she took the opportunity to question astrobiology in her blogs. As far as I know, astrobiology is a legit research area.

Disclaimer: Part time astrobiology student. She is stepping on my toes. I have quite right to take offense.

But there is no question about my larger motives which is to support fruitful science where I see it. Or I would start to attack microbiology, I guess.

Hmm, that's in isolation, not in organisms, which have many tricks up their sleeve. "a few species of bacteria are able to use arsenic compounds as respiratory metabolites." -http://en.wikipedia.org/wiki/Arsenic

There goes that theory.

It's certainly good to keep the logic straight. Based on what we know, is it impossible that an organism could replace phosphorous with arsenic? Certainly not - even though certain arsenic compounds are very unstable, organisms could find a way to stabilize them. So I believe a correct assessment of our current understanding is that we don't know of any organisms that substitute arsenic for phosphate. Based on what we know about chemistry, it seems unlikely that it could happen, but not impossible. No need to "withhold judgment". It's interesting to note that this "state of the field" is exactly that same as it was before the Wolfe-Simon paper.

With that partial quote I would agree, but the full quote would be ""The end result is that the fundamental biopolymers conserved across all forms of life remain, in terms of chemical backbone, invariant."

I have no trouble with that. The original Wolfe-Simon et al. claimed to have found variance in that chemical backbone. This paper shows that there is no proof of such variance. They don't say that its absolutely super-impossible that such variance would exist, just that the evidence doesn't support such conclusions. The major biopolymers indeed remain invariant in basic chemical structure.

Moreover, the context is the CHONPS core. I think we can predict CHNP use, with O & S maybe optional but very likely, both from a priori availability and from a posteriori usage. The energy constraint theorists would be adamant on the latter. [As in CHNP as well as later photosynthesis necessary parts of "collapse to life" energy use in metabolism, "Energy flow and the organization of life", Morowitz & Smith, 2006.]

To replace any of it would be both unlikely and difficult generally, and As has its own peculiar problems (hydrolysis, IIRC).